Non-invasive detection of subcutaneous tissues has concerned medical practitioners for many years. It is known by practitioners that many forms of subcutaneous tissue are responsive to electrical signals. Biologic, electrically responsive membrane systems (BERMS) are lipid bi-layers containing embedded protein molecules, some of which are ion channels. The density of embedded ion channels varies by tissue type, with nerve tissue having the highest concentrations of ion channels per gram of tissue. Nerve abnormalities, e.g., neuromas, have even higher concentrations of ion channels than normal nerve tissue. Other tissues, e.g., muscle, have lower densities than normal nerve tissue.
Prior art for noninvasive, electrically based, determination from the skin surface of tissue depth, composition, configuration, and/or state of function either detects a change in the function of the biological tissue structure in response to stimulation or assumes characteristics about electrical field paths in tissue. In one technique the location of nerve is detected by generating action potentials in nerves from certain electrodes within an array of electrodes.
U.S. Pat. No. 6,167,304 to Loos discusses the use of induced electrical fields to cause nerve “resonance.” It is unclear specifically what is meant by the term resonance in the Loos disclosure. This resonance occurs at certain frequencies and is associated with physiological findings. However, it is clearly not the same as the electrical phenomenon of resonance, which is a function of inductance and capacitance connected either in series or in parallel, with a resistance resulting in marked impedance changes at a single, unique frequency. The determination of impedance plays no role in the Loos resonance, which occurs at multiple frequencies.
U.S. Pat. No. 5,560,372 to Cory (herein incorporated by reference) teaches that, under certain conditions, the applied voltage required for maintenance of controlled current flow through skin surface electrodes is reduced when measured on skin over the position of peripheral nerves as compared to skin not overlying significant nerve tissue. This capability has not been addressed with other techniques, e.g., electrical impedance tomography (EIT). The device in Cory does not require action potential generation. This device indicated the lowest impedance site within its field by activating a single light emitting diode (LED) corresponding to the electrode contacting the skin surface at that site.
In the technique of EIT, current flow between a pair of electrodes causes simultaneous voltage, amplitude, phase, or waveform variations at other, non-current carrying electrodes arrayed on the body surface or in subcutaneous tissues, as described in U.S. Pat. No. 6,055,452 to Pearlman. Varying the electrode pairs through which current is flowing, followed by combining and analyzing the data, allows construction of specific impedance images that may be related to underlying structures. A key assumption for the performance of EIT is that tissues have unique electrical characterizations, the most important being the specific impedance, tissue resistivity, and tissue dielectric constant. The electrical field itself supposedly does not affect these parameters, although changes in organ size, content, conformation, or state of function are reflected in altered conductivity patterns. The technique of EIT analyzes voltage information from the skin surface at points distinct from the current carrying pair of electrodes. The assumption is made that tissue resistivities or dielectric constants are stable in the presence of these electrical fields, allowing the calculation of current flow patterns beneath the skin surface and construction of images from those patterns. In this technique, resolution and identification of subsurface structures remains a problem.
The recognition that tissue represents a non-homogeneous conductor best modeled as a parallel resistance and capacitance with a series resistance has enabled determination of the bulk conductor electrical properties of tissue. Below are listed notable research papers in this field establishing some of the physiological and technological foundation upon which the present invention is based:    1. Oaklander A L: The Density of Remaining Nerve Endings in Human Skin with and without Postherpetic Neuralgia after Shingles. Pain 2001; 92: 139-45;    2. McArthur J C, Stocks E A, Hauer P, Comblath D R, Griffin J W: Epidermal Nerve Fiber Density. Arch. Neurol. 1998; 55: 1513-20;    3. Petersen K L, Rice F L, Suess F, Berro M, Rowbotham M C: Relief of post-herpetic neuralgia by surgical removal of painful skin. Pain 2002; 98: 119-26;    4. Nolano M, Simone D A, Wendelschafer-Crabb G, Johnson T, Hazen E, Kennedy W R: Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation. Pain 1999; 135-45;    5. Hodgkin A L, Huxley A F: A Quantitative Description of Membrane Current and its Application to Conduction and Excitation in Nerve. J. Physiol. 1952; 117: 500-44;    6. Rall W: Core Conductor Theory and Cable Properties of Neurons, Handbook of Physiology, section 1, The Nervous System. Edited by Brookhart J M, Mountcastle V B, Kandel E R. Baltimore, Md., Baltimore, Md., 1977, pp. 39-97;    7. Finkelstien A, Mauro A: Physical Principles and Formalisms of Electrical Excitability, The Nervous System. Edited by Brookhart J M, Mountcastle V B, Kandel E R. Baltimore, Md., Waverly Press, Inc., 1977, pp. 161-213;    8. Mauro A: Anomalous Impedance, A Phenomenological Property of Time-Variant Resistance: An Analytic Review. Biophysical Journal 1961; 1: 353-72;    9. Cooper M S: Membrane Potential Perturbations Induced in Tissue Cells by Pulsed Electric Fields. Bioelectromagnetics 1995; 16: 255-62;    10. Sabah N H, Leibovic K N: Subthreshold oscillatory responses of the Hodgkin-Huxley cable model for the squid giant axon. Biophys. J. 1969; 9: 1206-22;    11. Mauro A, Conti F, Dodge F, Schor R: Subthreshold behavior and phenomenological impedance of the squid giant axon. J. Gen. Physiol. 1970; 55: 497-523;    12. Cole Kans., Baker R F: Longitudinal impedance of the squid giant axon. J. Gen. Physiol. 1941; 24: 771-88;    13. Cole K S: Rectification and inductance in the squid giant axon. J. Gen. Physiol. 1941; 25: 29-51;    14. Rudy Y, Plonsey R: The eccentric spheres model as the basis for a study of the role of geometry and inhomogeneities in electrocardiography. IEEE Trans. Biomed. Eng. 1979; BME-26: 392-9;    15. Cole K S: Electric impedance of suspensions of spheres. J. Gen. Physiol. 1928; 12: 29-36;    16. Cole K S: Electric impedance of suspensions of arbacia eggs. J. Gen. Physiol. 1928; 12: 37-54;    17. Cole K S: Electric phase angle of cell membranes. J. Gen. Physiol. 1932; 15: 641-9;    18. Cole K S, Hodgkin Ala.: Membrane and protoplasm resistance in the squid giant axon. J. Gen. Physiol. 1939; 22: 671-87;    19. Cole K S, Baker R F: Transverse impedance of the squid giant axon during current flow. J. Gen. Physiol. 1941; 24: 535-49;    20. Cole K S: Membranes, ions, and impulses. Berkeley and Los Angeles, University of California Press, 1972, pp. 1-569;    21. Cooper M S: Gap junctions increase the sensitivity of tissue cells to exogenous electric fields. J. Theor. Biol. 1984; 111: 123-30;    22. Gabriel C, Gabriel S, Corthout E: The dielectric properties of biological tissues: I. Literature survey. Phys.Med.Biol. 1996; 41: 2231-49;    23. Gabriel S, Lau R W, Gabriel C: The dielectric properties of biological tissues: II. Measurements in the frequency range 10 Hz to 20 GHz. Phys. Med. Biol. 1996; 41: 2251-69;    24. Gabriel S, Lau R W, Gabriel C: The dielectric properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues. Phys. Med. Biol. 1996; 41: 2271-93;    25. Rall W: Theory of Physiological Properties of Dendrites. Ann. NY Acad. Sci. 1962; 96: 1071-92;    26. Holder D S: Impedance changes during the compound nerve action potential: implications for impedance imaging of neuronal depolarisation in the brain. Med. & Biol. Eng. & Comput. 1992; 30: 140-6;    27. Jongschaap H C N, Wytch R, Hutchison J M S, Kulkami V: Electrical Impedance Tomography: A Review of Current Literature. Eur. J. Radiol. 1994; 18: 165-74;    28. Kwok G, Cohen M, Cosic I: Mapping Acupuncture Points Using Multi Channel Device. Australas. Phys. Eng. Sci. Med. 1998; 21: 68-72;    29. Lykken D T: Square-Wave Analysis of Skin Impedance. Psychophysiology 1971; 7: 262-75;    30. Kaslow A L, Lowenschuss O: Dragon Chasing: A New Technique for Acupuncture Point Finding and Stimulation. Am. J. Acupunct. 1975; 3: 157-60;    31. Reichmanis M, Marino A A, Becker R O: Electrical Correlates of Acupuncture Points. IEEE Trans.Biomed.Eng. 1975; BME 22: 533-532;    32. Johng H M, Cho J H, Shin H S, Soh K S, Koo T H, Choi S Y, Koo H S, Park M S: Frequency Dependence of Impedances at the Acupuncture Point QUZE (PC3). IEEE Eng. Med. Biol. 2002; 33-6;    33. Prokhovav E, Llamas F, Morales-Sanchez E, Gonzalez-Hemandez J, Prokhorav A: In Vivo Impedance Measurements on Nerves and Surrounding Skeletal Muscles in Rats and Human Body. Med. & Biol. Eng. & Comput. 2002; 40: 323-6; and            34. England J D, Happel L T, Kline D G, Gamboni F, Thouron C L, Liu Z P, Levinson S R: Sodium Channel Accumulation in Humans with Painful Neuromas, Neurology 1996; 47: 272-276.        
Accordingly, there exists a need to non-invasively detect tissue substructures in a sample which can accurately locate, identify, and discriminate the tissue substructures.